Papovaviruses are ubiquitous, usually nonpathogenic agents in human populations. Occasionally, however, these agents are associated with severe urological infection and, in rare immunocompromised hosts, with a fatal demyelinating infection of the central nervous system, progressive multifocal leukoencephalopathy (PML). There is also suggestive evidence that these agents may play a role in human neoplasia. Little is known about the pathogenesis of papovavirus infections in man or about the conditions which must be present for these agents to produce fatal neurological disease. The present proposal is submitted to allow transfer of the current research award from the University of Virginia to the University of Utah. The experiments proposed represent continuation of the research plan as outlined at the time of submission for competitive continuation from the University of Virginia at the 06-07 year of the award. Studies to be conducted over the coming year will continue investigation of the infection caused by a murine papovavirus, K virus, in its natural host, as a possible model for human infection. The experiments planned will employ immunocytochemical staining for K virus T and V antigens and in situ hybridization methods to study chronic and latent K virus infection. Additional experiments will be conducted to increase the infectivity of K virus for the central nervous system by brain-to-brain passage and to determine whether central nervous system infection can be produced by intracranial inoculation of mice with K virus-infected cells. During the coming year we will also attempt to purify K virus T antigen by immunoprecipitation and SDS-PAGE electrophoresis and will study host mechanisms required for maintenance of K virus latency. It is hoped that these studies will provide further information about the interaction of papovaviruses with their natural hosts and will help elucidate the pathogenesis of papovavirus infections in man.